1. Field of the Invention
The present invention relates to a method for making donepezil, especially to a method for making donepezil using a low-cost reducing agent, sodium dithionite (Na2S2O4), for shortening reaction time and improving safety.
2. Description of the Prior Art
Donepezil is one of the most important drugs for treating Alzheimer's disease and has been approved by FDA in 1996 under the brand Aricept®.
The conventional method for making donepezil starts with a reduction reaction by using (E)-2-((1-benzylpiperidine-4-yl)methylene)-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one (hereinafter denoted as “E2M”) as a precursor, whose structure is as shown in formula 1.

Donepezil, 2-((1-benzylpiperidine-4-yl)-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one, has a structure as shown in Formula 2.

With reference to U.S. patent publications 2007/0088055 and 2009/0253746, in these methods the “carbon=carbon” double bond of E2M is reduced to the “carbon-carbon” single bond of donepezil with catalyst. The catalysts used in the references are hydrogen gas (H2) and palladium (Pd)/aluminum(III) oxide (Al2O3), and hydrogen gas and platinum (Pt)/carbon (C) respectively, both of which allow hydrogen on the surface of a noble metal, palladium or platinum reducing the “carbon=carbon” double bond of E2M to the “carbon-carbon” single bond, resulting in donepezil.
Utilizing the conventional methods not only acutely raises safety concerns by employing hydrogen for reduction, but also raises the cost by using the noble metal such as palladium or platinum. In addition, the reaction times of the inefficient catalyzed reactions as disclosed in the aforementioned references are respectively 3 hours and 7 hours.
To overcome the shortcomings, the present invention provides a method for making donepezil to mitigate or obviate the aforementioned problems.